Contents

In May of 1994, I posted to a Usenet newsgroup an inquiry about the
interaction of LSD with antidepressants. At the time, I had a friend who
was interested in trying LSD, but she was concerned about its potential
interaction with Lithium, which she was taking to control a bipolar
disorder. My friend ended up never trying LSD.

Because there was, at the time, no other information on this subject
available online, I put the responses I received on a web site (which
is what you are now looking at) for the benefit of others. This resource
is expanded as new information and anecdotes continue to trickle in.

If you have another anecdote or something else to add, please write to me.

If you don't feel like reading this whole thing, here are the essential
points you need to know:

1. There is still very little legitimate, thorough medical research
on this subject. LSD's outlaw status makes it very difficult to
obtain permission & funding for research. Therefore, you should regard
all of the anecdotes and conclusions here as being scientifically unproven,
and you should note that any experimentation you choose to do carries a
significant risk.

2. Lithium or tricyclics (like Amitriptyline, Anafranil, Asendin, Aventyl,
Elavil, Endep, Norfranil, Norpramin, Pamelor, Sinequan, Surmontil, Tipramine, Tofranil,
Vivactil) are fairly consistently reported as being very bad in combination with LSD.
People attempting this combination are unable to communicate with others,
they go into "fugue states" where they end up in other places and don't know
how they got there, and they are generally in a terrible place psychologically.
Life-threatening seizures and at least one DEATH have been reported to be
triggered by the combination of LSD and lithium.

If you have an anecdote to share: email Mike Brown
<mike-lsd@hyperreal.org>
All email will be treated confidentially, and will be made anonymous if I decide
to incorporate it into this resource.

If you have a question about the interaction between a specific antidepressant
and popular psychedelics, or you'd like to contribute to legitimate medical
research on this topic: email Kit Bonson, Ph.D.
<kbonson@earthlink.net>
Kit has been studying the interactions between antidepressants
and psychedelics for a number of years at the National Institute of Mental Health.
If you or someone you know has info to contribute, she can send you a questionnaire
that they have been using to collect information. Your info might one day help
save a life, and don't worry -- all contributions are kept confidential.

If you are taking any medications whatsoever, consult your personal physician
before combining them with anything. Doctors have much information at
their disposal regarding the medications they prescribe, and what combinations
are relatively dangerous. Be honest with your doctor about what you put into your
body. Of course they won't like to hear that you're experimenting, but they may
be able to help reduce the risks you are taking by switching your prescription,
for example.

Each of these contributions came from people who claim to have some
kind of experience with LSD and antidepressant interactions. While the
subjective experiences described herein are not scientific, there does seem to
be a reasonable conclusion that one can draw from them: that it's
generally not a good idea to take LSD while under the influence
of antidepressants. You will either have difficulty experiencing the
usual effects of LSD, or you will enter a very bad psychological state.

General advice: LSD + lithium is risky

Not advisable. Potentially very dangerous.

If your friend is planning to do this, then she MUST research LSD
intensively before taking it...and get a good understanding of exactly
what risks she will be taking.

LSD has been known to 'trigger' latent mental illnesses - it doesn't
cause them, but it can exacerbate the condition - even if the person
doesn't yet know that they have any 'condition'. This is probably where
the myth that "lsd can make you crazy" originally came from.

On the other hand, hallucinogens can cause a profound change in
outlook...enough to lift a severe depression - I know that this can
happen because it happened to me when I was around 22 - I'm 27 now. I
attribute my current mental health, and even my continued existence, to
a batch of mushrooms I took when I was suicidally depressed - turned my
head around completely, and within a few weeks I was well on the road
to recovery. It wasn't an instantaneous, magic cure but it provided
the impetus that I needed to get started. I would probably have
topped myself within a few months otherwise - suicide was constantly
on my mind, and I was evaluating different methods trying to come to a
decision...no way to be sure, but I expect that I would be dead by now
if it weren't for that mushroom trip.

So, tell your friend to BE VERY VERY CAREFUL. LSD could teach her
something, or it could send her into a downward spiral.

LSD + bipolar cycles, no medication: A report of an apparent manic episode

I'm not sure if there are any known harmful interactions between LSD and
lithium. In fact, I don't think anyone is _sure_ why Lithium is effective
in stopping bipolar cycles.

However, I am SURE that LSD is not something that should be introduced to
anyone with manic-depressive disorder. My girlfriend is also bipolar, and
LSD will cause a triggering effect in her that sends her straight into
mania, almost immediately. All it took was one trip. She
had gone without an episode for more than 5 years until she decided to dose
one day. Can you imagine how unpleasant that must feel? Full blown mania
PLUS an acid trip (which would probably become a bad trip.)

I hate to be one of those types that perpetuates these drug horror stories,
but it's just not a good idea for anyone who has a clinical disorder to take
mood altering drugs. Clara actually had to drop out of school that semester
and seek treatment at a hospital she ended up staying at for six weeks.
Mind you, she wasn't being treated for "Post LSD psychosis" ( a condition
which is a complete myth in my opinion.) but for the mania which the LSD
catalyzed.

I've also had positive experiences with LSD, so I have no bias against it.
but please don't let your friend take it! If you do decide to
do it, keep a close eye on her! (as if you wouldn't :) )

A postulation that LSD counteracts stabilizing effects of Lithium

I've never heard of this exact situation before, but it seems like it Might
be dangerous to me.. Lithium, as I understand it is used to stabilize a
person's personality, to lop off the manic and the depressive parts , and
leave the person more level.. but LSD can really send a person reeling in
either direction quite quickly.. I wouldn't recommend that anyone with
mental problems severe enough to me medicated in the long term try LSD...

LSD + lithium: An observation of increased LSD tolerance

Generally I lurk here in alt.drugs for lack of pertinent info, but here I must
comment... I was diagnosed manic-depressive in March, and was put on lithium
soon after. Contrary to popular belief, being manic-depressive is not an "I'm
so out of control everyday" sort of problem. It comes and it goes, many people
go years without a significant episode of mania or depression.

I have combined my lithium with LSD and had no problems. The only effect I
noticed at all with a slight increase in my tolerance of LSD (previously I had
very little - when friends dropped 2 tabs, I dropped 1, etc.). The LSD didn't
swing me into a mania or depression.

However, this is my experience. In the drug books I've read, the warning with
mixing lithium with pot or LSD is "possible psychosis". although no one in any
manic-depressive support group or online group I've talked to has experienced
such.

I knew a guy last year, and I started hanging out with him. I soon relized
that he was heavily into drugs. He took several prescriptions, including
lithium, and I know he had dropped LSD many of times. Ever since Ive known
him hes seemed kinda "not all there", and the longer i knew him the worse
it got. About 2 months ago he was put in a "half-way" house. His mother
did not think he could take care of himself. I personally think he is gone
insane due to taking to many drugs. I just thought I would write and give
you my opionion.

LSD + Depakote: a report of no adverse side-effects

I am bi-polar manic depressive. I have been so all my life, but
have only recently been diagnosed. The doc recommended I take Depakote
instead of Lithium. I have also taken 380 doses of LSD in 4 years, which
is not counting the acid parties I attended before that. So far there
have been no adverse side effects, only positive effects(i.e., higher
I.Q., better grades and a new awareness of my conscious self). I cannot
offer any info on Lithium and LSD interactions, but advocate the use and
further study of LSD. Then again, I may be just an exceptional case.

LSD + lithium: a report of no adverse side-effects

I have been taking lithium for almost one year now. I started
last October after I experienced my first (and only to date) manic episode
of my life and was hospitalized. I had tripped four times before the
episode, all within a year of the episode. I have also tripped twice
since then, once in May and again in July. I did take smaller doses the
past two times, half a hit and three quarters respectively, but I would
say it was quite potent acid since I tripped for around 10 hours both
times. Also, all six of my experiences with LSD have been positive,
especially the last two.

I would like to finish with my opinion that both
LSD and manic-depression are EXTREMELY profound and powerful experiences
and I treat both with the respect that they deserve and I recommend that
you and your girlfriend do the same.

LSD + lithium: no adverse side-effects reported, but this person has
other problems...

lsd does exacerbate but only to show you what is wrong in order for you to
choose a different approach. lsd showed me my ego behaivior. It revealed
that was otherwise suppresed. I recognized the importance of caring. and
accknowlgeing god and that my way is not real only imagined.

I never really figured out a way to change my energy consuming thinking
which is the cause of my disoroder, mania) the time I had some bad acid.
How it effected me and what happened when I went back on lithium and what
I did to fix it. what my problems with acid are and how I solve them. how
to never be bored with lsd. shrooms and their advatages and how they
differ from lsd. Lithium what it does for me. lithium and brian's lsd
expierence. lsd should be few and far between and why.

LSD for self-medication of schizoaffective disorder and severe
depression: a report that it might hurt more than it helps

I lost a loved one to a suicide in October of 1998. It hurts in ways
that words can not describe. Since his death, we have learned that
before we got professional help for him, he tried to solve his own
problems himself and using LSD was one of the chemicals that were
used. I read a study that reported that if one has predisposed
tendencies for schizophrenia and related mood disorders, LSD can help
bring on the emergence of the symptoms. Our loved one had been
diagnosed with schizoaffective disorder and had suicidal ideations
present in October of 1997. When one of your readers asked about
using lithium with LSD, I felt compelled to write. Talk to your
parents or loved ones. We are part of your treatment team and want to
help. Now it is over for us. We can not help him.

LSD + lithium: a report of positive side-effects

yeah dude. yur friend can trip and use lithium at the same time her trip
will just b a lot better. ive done it b fore infact a few times

Editor's Note: Take this with a grain of salt, obviously. Dude.

LSD + various antidepressants: a report of no adverse side-effects

I'm a manac-depressant, ere, I have Bi-polar disorder. I've taken drugs on
Depakote, Zoloft, lithium, Wellbutrin, Ritalin, Prozac, and Toferrinal. They
all say not to mix with alcohol or other drugs. But what the hell, they mix
each other up without a problem. I've been on at the most, 3 of these drugs
and either drank plenty of alcohol, smoked plenty of reefer, tripped my
fuckin' balls off, or a combonation of all three along with three of the other
drugs. I'm still alive and taking my meds. regularly and attending school and
getting above a 3.0. I say, let your friend trip her brains out. Just make
sure you are tripping with her so that way she doesn't get some kind of crazy
trip where she wigs bad. A peson with bi-polar and a bad trip don't mix too
good. I just had one for the first time about a month ago. I never thought
I'd have a bad trip until that night. The imagination and loss of reality can
be twice as bad in a person suffering depression. It could bring out the
worst in the mind. But as long as you are with your friend, she'll be fine.

A friend of mine was a normal kinda guy until one mushroom trip sent him out
of control into a kind of bi-polar disorder, he is now on arapax and had had
no contact with any form of drugs until he had a smoke with us not long ago.
One session sent him into an episode in which he hid behind a heater from us
as he thought we were going to kill him. He is no longer using any form of
illegal drugs. Another friend suffered an episode of bi-polar disorder after
an acid trip and is now also on valium and arapax and has no problems with
pot or LSD. I am on amytriptylene and despite having taken acid and smoking
pot regularly, have suffered no ill effects, if anything, i feel a lot
better for having taken them. Drugs seem to have lifted me out of several
suicidal episodes throughout my life.

However, given that i know of at least 4 people who have come to suffer from
bi-polar disorder bought on by a single LSD trip i would definately not
reccomend it for someone who is already suffering from this disorder, it
seems that it would be likely to bring it on worse. In saying this, there is
also the chance it could turn it completely around in the same way it brings
these episodes on. It really depends whether it is worth the experiment,
given that someones mental health is at risk.

i had bi-polar problems long before i started taking any medication. long
before i started taking medication i took LSD, and i swore i finnally found
out how to feel "normal". once i was on medication [PAXIL] i found that LSD
did not work the same for me. weird, huh?

LSD + lithium: a report of seizures

I Am Bipoler Like You Friend.
I Also Take Lithieum
And LSD Has Ben Realy Bad While On It.
I Sugest That A Person On Lithum Stop Taking 2 Days Befor Thay "TRIP"
I Dident Once And I Almost Died! So So Bad I Was In The ER Intensif Care And
Haveing Convolstions So If You Whant To Trip And Are Takeing Lithieum Stop
Taking It For Atleast 2 Days!
If You Whant To Hear The Hole Storey E-mail Me Back!

Editor's Note: I don't make up this stuff.

LSD + lithium + Prozac: a report of hospitalization

ive got a friend who was prescribed to lithium and prozac. he dropped some
acid and then took his pills while he was trippin, he wound up goin to the
hospital. i dont know if it was the lithium or prozac, most likely the
prozac.

LSD + various bipolar disorder medications: a report of no negative side-effects

hey ok um i have bi polar disorder im on a shit load of medications and i
take lsd and ecstasy all the time and my life has been better my parents
trust me more and my grades have gone way up i think im smarter so like your
friend should take lsd just watch her you know

High doses of LSD + lithium + Wellbutrin: a report of no negative side-effects

I was diagnosed with bipolar disorder 3 years ago and have been taking
lithium and antidepressants since. I am presently taking Wellbutrin along
with lithium. I tried lsd several months ago, and have taken it twice since,
4 hits the second time and 5 the last. Pschologically, I didn't see a
terrible danger, only slight paranoia that the trips would never end. Also,
my last trip lasted about 20 hours. Personally, I wouldn't recommend lsd to
anyone, since everyone's reactions are different, but to say I didn't enjoy
it would be a lie.

LSD + lithium: a report of severe dissociation and seizures

I take the drug Lithium for
bi-polar disorder and I had taken it the night before i dropped 2 hits of
acid. It was my 3rd time doing LSD and i was already worried about the
effects of the 2 drugs together because the 2 previous times i was not on
lithium. The trip was a very bad trip. It was completely auditory, giving
me a schizophrenic-like feeling which was very strange, but, it wasn't 3
hours after i dropped that i started to go into a seizure. (I do not have a
history with epilepsy or seizures of any kind). I went unconscious and,
thank God, I had a sober friend their to help. After I came to, I was
completely in an altered state for another 2 or 3 hours, barely conscious,
still hearing voices all around me but seeing no visuals and then going into
another seizure, this time i almost stopped breathing and my jaw locked down
hard enough that i subconciously bit the sides of my tongue off. When I
woke up from that I threw up, which isn't odd for someone who has taken a
large dose of the drug, and it was through. Not even aftereffects of the
drug like i usually experienced before. I have not had any flashbacks since
then, and I seem to be fine, but i do not recommend mixing the two drugs
together, at all.

High dose of LSD + lithium: a report of a possible seizure, followed by
death.

I can prove that lithium and LSD do not interact well. Two weeks ago, a
friend died while on a small dose of Lithium and a fairly large dose of LSD.
He was Bi-polar and only on the medication for about four weeks. It looked as
if he went into a downward spiral, then possibly have had a seizure. There
were no other toxins in his blood, according to the coroner. Please do not
mix these two powerful drugs, it's not worth the trouble and it's a gamble
either way. If you do decide to take that gamble, then make sure someone
sober is with you.

Editor's Note: This is the first time we have heard of a
death resulting from this combination. I'm seeking more info from the
contributor of this anecdote.

High dose of LSD + lithium: a report of severe dissociation and hospitalization

I had an experience 5 years ago when I was taking the
drug Lithium for manic depression. I took 4 more
pills of Lithium than I was supposed to take that
night because I was depressed. I was at a party and
smoking a lot of weed, I was also drinking alcohol,
about 8 beers already. One of my friends came over
and had some acid so I bought 50 hits for a very good
price. I took two and about an hour later I didn't
feel anything so I dropped 5 more to get this drug
moving. Not to long after that I was sitting on the
couch talking to a group of friends when I just
started puking all over myself (talk about
embarrassment) and ran to the bathroom. I got help from
my friends and took a shower while the party is still
going on. When I got out I started talking to people
that weren't there and the walls, I sat down for a few
minutes or a lot don't really know. I got up and that
is all I remember. I woke up a few hours later in the
hospital. It was weird, hours were going by like
minutes. I was hospitalized for a few days, but it
sucked, I don't know if it was the mixture of
everything or what, but the doctor told me that no
drug should be taken with Lithium, but of course I
didn't listen.

LSD + lithium: a report of a seizure and heart attack

I almost died this weekend, and it was a result of mixing LSD with Lithium.
I am bipolar and take Lithium. I was at a rave this weekend and had two hits
of acid (which I heard were rather strong hits). I ended up having a
seizure, foaming at the mouth, thrashing around (I have bruises all over my
arms and legs now), and I turned blue in the face before anyone called 911.
I later experienced cardiac arrest, where my heart stopped beating and I
basically "died" for a little while before they brought me back to life.
SCARY SHIT!!! I would not recommend it. If I had only known how deadly
mixing LSD with Lithium was beforehand. I really hope someone reads this and
learns from my story.

Not only did I almost die, but all my "friends" in the drug culture have
dropped me totally. They won't even talk to me anymore. These were people I
really thought were my friends. There were people at the rave (at people's
apartment) who didn't even want to call 911 for fear that they would get
busted for drugs.

Just be careful what drugs you do and who you do them with. It's hard to
know who to trust.

LSD + lithium + Zoloft: no details, but it was apparently very bad

I did LSD recently while currently taking 900 mgs of lithium and 50 mgs of
Zoloft. I WILL NEVER TAKE LSD AGAIN!!!

LSD + lithium: a report of psychosis and hospitalization

LISTEN TO ME! DO NOT MIX LITHIUM AND LSD. I have tripped countless times
in my life and always maintained complete control. I tried it once on
Lithium. I woke up in a hospital two days later. The police found me
wandering around in an "acute psychotic episode". I was running into trees
headfirst and trying to walk through physical objects. The doctors told
me that if the police had found me an hour later, I would have been dead
or a vegetable for the rest of my life. I lucked out by having the cops
find me. Yes, I was expelled from my college, but am still alive and
somewhat sane. Please learn from my mistake!

A high dose of LSD + Celexure: a report of a seizure
A high dose of LSD + Zoloft: a report of no adverse side-effects

hi i am writin to you because recestly me and a couple of friend were
goin to the city to see alazer show and right after we got of the train
my friend colapsed and had a sisure she took 3 tabs it was a scary sight
she on celexure an anideppesant and i take zoloft and took 5 tabs and i
didnt have a sisure

I am taking wellbutrin for depression, I
take 2 150 mg SR (slow release) pills a day. I have tripped once on
mushrooms, loved it, was a positive experience. I tripped on LSD once, same
thing, although the changes in my mind seemed more permanent than mushrooms.
Although last night I tried LSA (similar to LSD) (morning glories (heavenly
blue)) and I did not feel suicidal, but thought that my life was going to
come to an end, like the perfect ending of a movie, I felt my thought
processes changing and I could not tell if what was happening was good or
bad, it was just really wierd. I experiened nausea and actually came to a
point where I felt like I had become a girl, I'm male, I can't explain that,
(no, I do not think men are superior) then I felt weak, this was a few
minutesd after I had felt invincible. When I came home I decided to go
online to see if I could tell what was happening, I surely could not
understand it. Then I found an article telling me that commercial seeds are
treated with POISON that caused nausea and vomiting to discourage abuse, it
also told me that to much of this poison could psychotic reactions, and at
times I did feel a little psycho.

I have had horrific
experiences with lithium and lsd. I was placed on
lithium three years ago for bipolar disorder. Prior
to this i had taken at least 150 doses of lsd, with
absolutely no bad experiences. After taking 900 mg of
lithium a day for three months or more, I dosed two
hits of weak blotter. The trip spiralled out of
controll, much more intense and all-encompassing than
should be possible with that dosage, and the seven
people with me, who had taken just as much or more,
were having mild trips with nothing more exciting than
tracers. I began hallucinating the sounds of hundreds
of chainsaws, all around me, and that's the last thing
I remember. Later, I was told that I fell to the
ground and began convulsing, and was taken by
ambulance to the er where I woke up within half an
hour or so, was given back my urine-soaked clothing,
and driven home. I assumed that the seizures had been
a result of a bad trip and the hospital personnel
didn't give too much consideration to one more
acid-head rolling through, so they didn't have much to
say to me one way or another so, being incredibly
stupid, I thought that I could still trip and be fine,
that it was a fluke. A month later I took two more
hits of blotter with old high school friends and went
to the park. It was a wonderful, warm, fantastic
experience until I began seizing. This time the
paramedics got there just as I swallowed my tongue,
and I had at least 28 seperate grand mal seizures
before they finally administered the last-ditch
possiblility, a paralytic so strong it stopped my
diaphragm so when i woke up this time I was on life
support and unable to move so much as my eyelids. Of
course, I blacked out again.

I no longer take lithium, am no longer considered
manic depressive, but I am so terrified of lsd that I
won't even kiss my boyfriend when he's tripping. I
know that there is an overwhelming possiblity that it
was merely the interaction of the lithim and the acid
that caused my brain to short out, but the hell if I'm
going to take that chance. I think that anyone taking
any sort of psychoactive chemical needs to do a lot of
research before mixing it with any other.

Abstract: This study investigates the possible interactions of
antidepressant agents and hallucinogens in humans through structured
interviews using a standardized questionnaire. Volunteer subjects
recruited through announcements placed on the Internet or other sources
were asked to describe the somatic, hallucinatory, and psychological
effects of self-administered LSD prior to and during chronic
administration of an antidepressant. Twenty-eight out of 32 subjects (88%)
who had taken an antidepressant with inhibitory effects on serotonin
(5-HT) reuptake (fluoxetine, paroxetine, sertraline, trazodone) for over 3
weeks had a subjective decrease or virtual elimination of their responses
to LSD. An additional subject who had taken fluoxetine for only 1 week had
an increased response to LSD. These data are in contrast to our previous
study that reported increased responses to LSD during chronic
administration of tricyclic antidepressants or lithium. Possible
mechanisms of action for the effects from serotonergic antidepressants
involve 5-HT2 and 5-HT1A receptors, changes in extracellular brain
serotonin concentrations, and changes in brain catecholamine systems.

Abstract: This study sought to investigate possible interactions
between antidepressant agents and lysergic acid diethylamide (LSD) in
humans through the use of retrospective questionnaires. Ten subjects were
identified who used LSD during chronic (3 weeks or longer) periods of
antidepressant administration. These subjects were asked to describe the
phenomenological effects of self-administered hallucinogens prior to and
during antidepressant treatment; a structured, standardized questionnaire
was used to evaluate LSD experiences. Chronic tricyclic antidepressant
administration was associated with subjective increases in physical,
hallucinatory and psychological responses to LSD. Similarly, subjects
receiving lithium chronically also reported increases in their responses
to LSD. In contrast, subjects who had been chronically taking an monoamine
oxidase (MAO) inhibitor reported subjective decreases in the effects of
LSD. This is similar to a previous report by our group of a decreased
response to LSD in individuals who were chronically taking
serotonin-selective antidepressants. These altered responses to LSD most
likely involve differential changes in central serotonin and dopamine
receptor systems and are consistent with other recent data suggesting that
the clinical efficacy of different classes of antidepressants may not
necessarily rely on a common mechanism of action in the brain.

Abstract: Two adolescents with a long history of abuse of
lysergic acid diethylamide (LSD) and symptoms consistent with major
depressive disorder, on initiation of antidepressant therapy with
selective serotonin reuptake inhibitor agents, had the new onset or
worsening of LSD flashback syndrome. The similarity in neuroreceptor
physiology for both LSD and serotonin suggests that the LSD flashback
syndrome may be induced by these drugs in patients with a history of LSD
abuse.

Article Title: On the central antiserotonin action of trazodone.

Article Source: Pol J Pharmacol Pharm 1979 Jan-Feb;31(1):25-33

Author(s): Baran L; Maj J; Rogoz Z; Skuza G

Abstract: Trazodone, an antidepressant drug with an unknown
mechanism of action, has been examined in order to demonstrate its central
antiserotonin action. Trazodone antagonizes the head twitch response
induced by 5-hydroxytryptophan in rats and mice, or by-5-methoxytryptamine
in rats (the ED50 values are 9.3, 5.2, and 10.8 mg/kg respectively). It
counteracts convulsions induced by tryptamine in rats (ED50=3.75 mg/kg).
Trazodone abolishes hyperthermia induced by serotoninomimetics (LSD,
quipazine, fenfluramine) in rabbits. It does not affect ptosis induced by
reserpine, and diminishes stimulation of the locomotor activity induced by
amphetamine. Our findings demonstrate that trazodone has a central
antiserotonin action, similarly as three other antidepressant drugs:
mianserin, danitracen and doxepin, whose central antiserotonin action has
been found previously.

Abstract: The antidepressant drug-Doxepin (DX) was examined in
order to investigate its central antiserotonin activity. The drug
antagonized the behavioral syndrome elecited by L-5-hydroxytryptophan in
rats and mice, but did not affect the pinna reflex. In the flexor reflex
preparation, DX acted like other sero-tonin receptor blockers: By itself,
it had no influence on the flexor reflex but it prevented the potentiation
induced by serotonergic agents (fenfluramine, LDS, mescaline). The
hyperthermia provoked by serotonergic agent (fenfluramine, LSD)in rabbits
was antagonized by DX. DX abolished the syndrome induced by oxotremorine.
The results obtained indicate that DX blocks central 5-HT receptors, like
the two other antidepressants, mianserin and danitracen.

Article Title: Effect of chronic tricylic antidepressant
treatment on the serotoninergic autoreceptor: a microiontophoretic study
in the rat.

Abstract: Chronic treatment with tricyclic antidepressant (TCA)
drugs has been shown to enhance the responsiveness of rat forebrain
neurons to serotonin (5-HT). In the present study, imipramine (5 mg and 10
mg/kg), iprindole (2.5 mg/kg), desipramine and femoxetine (5 mg/kg) were
administered daily for 14 days. The response of dorsal raphe neurons to
intravenous injection of LSD (4 microgram/kg) and to microiontophoretic
applications of 5-HT and LSD was assessed 24 h after the last dose. The
responsiveness to intravenous LSD and the effectiveness of
microiontophoretic applications of 5-HT and LSD were not altered by TCA
drug pretreatments. Furthermore, the treatments did not change the mean
firing rate of these 5-HT neurons. Those results suggest that chronic
treatment with TCA drugs does not alter the sensitivity of the 5-HT
autoreceptor. Thus, the effect of the previously reported increase of
postsynaptic neuron responsiveness to 5-HT would not be dampened by a
decreased activity of the presynaptic neurons.

Abstract: The model of LSD potentiated apomorphine hypermotility
[5] was used to classify different atypical antidepressants (danitracen,
mianserin, cyproheptadine) and pizotifen. All drugs have been shown to
inhibit specifically the locomotor activity potentiating effect of LSD in
a low dosage range (0.1-0.5 mg/kg i. p.) without influencing the
apomorphine effect. Since there is some evidence that the effect of LSD is
due to the inhibition of the activity of serotonergic raphe neurons, the
marked antagonizing effects of danitracen, mainserin, cyproheptadine and
pizotifen are regarded to be an expression of pronounced antiserotonin
activity.

Abstract: Alterations in platelet 5-HT2A receptor
characteristics have been reported in major depression as well as in other
psychiatric diseases, and some effort has been made to utilize platelet
5-HT2A receptor status as a biological correlate to antidepressant drug
response. In order to investigate whether treatment with a selective
serotonin reuptake inhibitor affects platelet 5-HT2A receptors, we have
studied platelet [3H]lysergic acid diethylamide ([3H]LSD) binding in
healthy subjects treated with fluvoxamine in increasing dosage once weekly
for 4 weeks. After 1 week of fluvoxamine treatment (25 mg/day), both Bmax
and Kd were significantly lower than before the start of the treatment
(19.9 versus 25.5 fmol/mg protein, P = 0.005 for Bmax; 0.45 versus 0.93
nM, P = 0.006 for Kd). Bmax returned to baseline during week 2, whereas Kd
was lower than the baseline value throughout the treatment period. After
discontinuation of fluvoxamine treatment, there was a significant increase
in Kd (0.50 nM before discontinuation vs. 1.14 nM after discontinuation; P
= 0.001), but not in Bmax. The study demonstrates that fluvoxamine affects
platelet 5-HT2A receptor status irrespective of underlying psychiatric
disease, and that this effect is evident already after 1 week at a
subtherapeutic fluvoxamine dose.

Abstract: Sleep deprivation (SD) is an effective, however
short-lived, method of treatment of depression. Preliminary findings
suggest that the antidepressive effect of sleep deprivation is mediated by
serotoninergic (5-HT) mechanisms. We therefore assessed serotoninergic
activity before and after total SD (TSD) as well as after the following
night sleep by investigating platelet LSD-binding, MAO B-activity, and
5-HT-content as well as plasma norepinephnne (NE) in 10 healthy men (age:
27.4 +/- 2.8 years). Blood samples were drawn on three consecutive days at
0700, 1300 and 1900 h, respectively. After TSD, a significant increase of
LSD-binding KD and Bmax as well as of MAO-B KM and plasma NE could be
observed, which, however, vanished after consecutive night sleep. Our
findings favour an increased serotoninergic transmission after TSD and
thus support the hypothesis, that sleep deprivation exerts its
antidepressant effects by pro-serotoninergic mechanisms.

Abstract: Chronic treatment with phenothiazines and
thioxanthenes has been found to enhance 5-HT-induced aggregation of human
platelets. A method has been developed to study 5-HT2 receptor binding
sites on platelets utilising [3H]-LSD and more recently 125I/LSD. Results
are presented which suggest that the LSD binding site is indeed the 5-HT2
binding site and that the LSD binding characterises the specific receptor
responsible for 5-HT-induced shape change and aggregation. In a group of
patients receiving phenothiazines or thioxanthenes, the Bmax of LSD
binding was increased. The mean binding affinity was decreased possibly
due to a persistence of neuroleptic in the platelet membrane preparation.
Analysis showed that this was not the reason why the mean binding capacity
was increased. The results show that chronic phenothiazine and
thioxanthene delta treatment 'up-regulates' platelet 5-HT2 binding sites
and that this may be accompanied by increased sensitivity to platelet
aggregation by 5-HT. In normal subjects desipramine treatment increased
the Bmax of platelet LSD binding and this was accompanied by an increased
prolactin response to tryptophan which is thought to be mediated by
central 5-HT function.

Article Title: Effects of antidepressant drugs on different
receptors in the brain.

Article Source: Eur J Pharmacol 1981 Mar
26;70(3):393-407

Author(s): Hall H; Ogren SO

Abstract: Radioligand receptor binding techniques were used to
characterize the effects of different structural types of antidepressant
drugs on neurotransmitter receptors. The tricyclic antidepressants more or
less potently inhibited the binding to rat brain preparations of several
different radiolabelled ligands [3H]WB4101, [3H]QNB, [3H]-d-LSD,
[3H]mepyramine). The potency of the nontricyclic antidepressants varied
greatly. Mianserin, potently displaced [3H]mepyramine, [3H]d-LSD and
[3H]WB4101 while it was very weak on [3H]QNB-binding. Nomifensine and the
specific 5-HT uptake inhibitors zimelidine and alaproclate had very low
affinity for these receptors. All the antidepressants tested were
practically devoid of activity on [3H]DHA binding, [3H]spiroperidol
binding, [3H]flunitrazepam binding, [3H]muscimol binding and [3H]naloxone
binding. The implications of these findings for biogenic amine theories of
affective disorders are discussed.

Article Title: Reevaluation of the indoleamine hypothesis of
depression. Evidence for a reduction of functional activity of central
5-HT systems by antidepressant drugs.

Abstract: The effects of antidepressant drugs on central 5-HT
receptor activity were studied in rats and mice. Antidepressant drugs were
evaluated for their ability to displace 3H-5-HT and 3H-d-LSD from membrane
binding sites in the dorsal neocortex of rats in vitro and for their
ability to block 5-HTP and d-LSD induced behavioral effects in mice. The
degree of blockade of head-twitches in mice produced by the
antidepressants was highly correlated with their affinity for 3H-d-LSD
binding sites. A number of antidepressant drugs such as amitriptyline,
nortriptyline, mianserine, doxepine, nomifensine and dibenzepine appear to
possess marked 5-HT receptor blocking activity at some type of 5-HT
receptors in brain. New antidepressant drugs such as zimelidine, which
specifically inhibit 5-HT reuptake and do not block 5-HT receptor sites,
may after chronic treatment also reduce the functional activity of 5-HT
systems by producing adaptive changes in postsynaptic 5-HT mechanisms.
Thus, a new indoleamine hypothesis of depression is presented: the
therapeutic action of antidepressant drugs may in part be due to a reduced
functional acitivity of some central 5-HT systems.

Abstract: The binding of [3H]LSD to serotonergic sites in human
brain was studied. The pharmacological profile of [3H]LSD binding in
frontal cortex differed to that in hippocampus. Analysis of the inhibition
of [3H]LSD binding by serotonin and spiperone was consistent with the
presence of two binding sites, which differed in pharmacological
specificity. The results are discussed in relation to previously published
findings in experimental animals.